Impact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure.

TitleImpact of minority nonnucleoside reverse transcriptase inhibitor resistance mutations on resistance genotype after virologic failure.
Publication TypeJournal Article
Year of Publication2013
AuthorsLi JZ, Paredes R, Ribaudo HJ, Kozal MJ, Svarovskaia ES, Johnson JA, Geretti AMaria, Metzner KJ, Jakobsen MR, Hullsiek KHuppler, Ostergaard L, Miller MD, Kuritzkes DR
JournalJ Infect Dis
Volume207
Issue6
Pagination893-7
Date Published2013 Mar 15
ISSN1537-6613
KeywordsAdult, Anti-HIV Agents, Benzoxazines, Drug Resistance, Viral, Female, Gene Dosage, Genotype, HIV Infections, HIV-1, Humans, Male, Multivariate Analysis, Mutation, Nevirapine, Reverse Transcriptase Inhibitors, Treatment Failure
Abstract

Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants increase the risk of virologic failure for first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We performed a pooled analysis to evaluate the relationship between NNRTI-resistant minority variants and the likelihood and types of resistance mutations detected at virologic failure. In multivariable logistic regression analysis, higher NNRTI minority variant copy numbers, non-white race, and nevirapine use were associated with a higher risk of NNRTI resistance at virologic failure. Among participants on efavirenz, K103N was the most frequently observed resistance mutation at virologic failure regardless of the baseline minority variant. However, the presence of baseline Y181C minority variant was associated with a higher probability of Y181C detection after virologic failure. NNRTI regimen choice and preexisting NNRTI-resistant minority variants were both associated with the probability and type of resistance mutations detected after virologic failure.

DOI10.1093/infdis/jis925
Alternate JournalJ. Infect. Dis.
PubMed ID23264671
PubMed Central IDPMC3571444
Grant ListK24 RR016482 / RR / NCRR NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
U01 AI042170 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States